Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation

Jeoffrey Pelletier; Marielle Balzano; Jérôme Destin; Camille Montersino; Marjorie C Delahaye; Tony Marchand; Anne-Laure Bailly; Florence Bardin; Emilie Coppin; Armelle Goubard; Remy Castellano; Marjolein J W de Bruijn; Jasper Rip; Yves Collette; Patrice Dubreuil; Karin Tarte; Cyril Broccardo; Rudi W Hendriks; Claudine Schiff; Norbert Vey; Michel Aurrand-Lions; Stéphane J C Mancini

doi:10.1016/j.isci.2023.106385

Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation

iScience. 2023 Mar 11;26(4):106385. doi: 10.1016/j.isci.2023.106385. eCollection 2023 Apr 21.

Authors

Jeoffrey Pelletier¹, Marielle Balzano¹, Jérôme Destin², Camille Montersino¹, Marjorie C Delahaye¹, Tony Marchand², Anne-Laure Bailly¹, Florence Bardin¹, Emilie Coppin¹, Armelle Goubard¹, Remy Castellano¹, Marjolein J W de Bruijn³, Jasper Rip³, Yves Collette¹, Patrice Dubreuil¹, Karin Tarte², Cyril Broccardo⁴, Rudi W Hendriks³, Claudine Schiff⁵, Norbert Vey^{1

6}, Michel Aurrand-Lions¹, Stéphane J C Mancini^{1

2}

Affiliations

¹ Aix Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France.
² University Rennes, INSERM, EFS, UMR S1236, Rennes, France.
³ Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
⁴ Centre de Recherche en Cancérologie de Toulouse, INSERM UMR-1037, Université de Toulouse III Paul Sabatier, Toulouse, France.
⁵ Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.
⁶ Department of Hematology, Institut Paoli-Calmettes, Marseille, France.

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) reflects the malignant counterpart of developing B cells in the bone marrow (BM). Despite tremendous progress in B-ALL treatment, the overall survival of adults at diagnosis and patients at all ages after relapse remains poor. Galectin-1 (GAL1) expressed by BM supportive niches delivers proliferation signals to normal pre-B cells through interaction with the pre-B cell receptor (pre-BCR). Here, we asked whether GAL1 gives non-cell autonomous signals to pre-BCR⁺ pre-B ALL, in addition to cell-autonomous signals linked to genetic alterations. In syngeneic and patient-derived xenograft (PDX) murine models, murine and human pre-B ALL development is influenced by GAL1 produced by BM niches through pre-BCR-dependent signals, similarly to normal pre-B cells. Furthermore, targeting pre-BCR signaling together with cell-autonomous oncogenic pathways in pre-B ALL PDX improved treatment response. Our results show that non-cell autonomous signals transmitted by BM niches represent promising targets to improve B-ALL patient survival.

Keywords: Biological sciences; Cell biology; Molecular biology.